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      Increased expression of endothelial lipase in symptomatic and unstable carotid plaques

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          Abstract

          The aim of this study was to evaluate endothelial lipase (EL) protein expression in advanced human carotid artery plaques (HCAP) with regard to plaque (in)stability and the incidence of symptoms. HCAP were collected from 66 patients undergoing carotid endarterectomy (CEA). The degree of plaque (in)stability was estimated by ultrasound and histology. In HCAP sections, EL expression was determined by immunostaining and the intensity was assessed on a semi-quantitative scale (low: <25%, high: >25% positive cells). Monocytes and macrophages in adjacent HCAP sections were stained with a CD163 specific antibody. High EL staining was more prevalent in histologically unstable plaques (in 33.3% of fibrous plaques, 50% of ulcerated non-complicated plaques and 79.2% of ulcerated complicated plaques; χ 2 test, p = 0.004) and in the symptomatic group (70.8 vs. 42.9% in the asymptomatic group; χ 2 test, p = 0.028). The majority of EL immunostaining was found in those HCAP regions exhibiting a strong CD163 immunostaining. EL in HCAP might be a marker and/or promoter of plaque instability and HCAP-related symptomatology.

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          Most cited references31

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          A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

          This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesion progression. The initial (type 1) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).
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            Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis.

            Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of inflammation, ie, interleukin (IL)-6, are elevated in patients with acute coronary syndromes and may contribute to the exacerbation of atherosclerosis. To assess the role of IL-6 in atherosclerosis, ApoE-/--IL-6-/- double-knockout mice were generated, fed a normal chow diet, and housed for 53+/-4 weeks. Mortality and blood pressure were unaltered. However, serum cholesterol levels and subsequent atherosclerotic lesion formation (oil red O stain) were significantly increased in ApoE-/--IL-6-/- mice compared with ApoE-/-, wild-type (WT), and IL-6-/- mice. Plaques of ApoE-/--IL-6-/- mice showed significantly reduced transcript and protein levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase (by reverse transcriptase-polymerase chain reaction and immunohistochemistry). Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into the atherosclerotic lesion was significantly reduced in ApoE-/--IL-6-/- mice. The transcript and serum protein (ELISA) levels of IL-10 were significantly reduced. Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque formation in ApoEK-/--IL-6-/- mice and leads to maladaptive vascular developmental processes. These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis.
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              A novel endothelial-derived lipase that modulates HDL metabolism.

              High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease. At least 50% of the variation in HDL cholesterol levels is genetically determined, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism and the HL (LIPC) locus has been associated with variation in HDL cholesterol levels in humans. We describe here the cloning and in vivo functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells in vitro and thus has been termed endothelial lipase (encoded by the LIPG gene). EL is expressed in vivo in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and in vivo effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.
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                Author and article information

                Contributors
                +385-91-5033747 , +385-91-3768286 , vdegoric@mef.hr
                +43-316-3804193 , +43-316-3809615 , sasa.frank@medunigraz.at
                Journal
                J Neurol
                Journal of Neurology
                Springer-Verlag (Berlin/Heidelberg )
                0340-5354
                1432-1459
                13 August 2011
                13 August 2011
                March 2012
                : 259
                : 3
                : 448-456
                Affiliations
                [1 ]University of Zagreb School of Medicine, Zagreb, Croatia
                [2 ]Department of Medicine, Sisters of Mercy University Hospital, Vinogradska 29, 10000 Zagreb, Croatia
                [3 ]Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/III, 8010 Graz, Austria
                [4 ]University of Zagreb School of Dental Medicine, Zagreb, Croatia
                [5 ]Ljudevit Jurak University Department of Pathology, Sisters of Mercy University Hospital, Zagreb, Croatia
                [6 ]Department of Surgery, Sisters of Mercy University Hospital, Zagreb, Croatia
                [7 ]Institute of Cell Biology, Histology and Embryology, Center of Molecular Medicine, Medical University of Graz, Graz, Austria
                [8 ]Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
                [9 ]Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
                Article
                6198
                10.1007/s00415-011-6198-3
                3296002
                21842303
                24e1d973-6f2e-4cf4-a12b-77e0b2875244
                © The Author(s) 2011
                History
                : 15 April 2011
                : 24 June 2011
                : 19 July 2011
                Categories
                Original Communication
                Custom metadata
                © Springer-Verlag 2012

                Neurology
                atherosclerosis,high density lipoprotein,endothelial lipase,inflammation,macrophages,carotid artery plaque

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